Exposure to organophosphates (OPs) in the form of nerve agents (e.g. sarin, soman and VX) and pesticides (e.g., paraoxon, parathion and malathion) may result in acute cholinergic effects by inhibition of acetylcholinesterase (AChE), permitting continuous firing of neurons and thereby producing toxicity, behavioral deficits and death. Of late, such agents pose an ever increasing military and civilian threat due to heightened terrorist activity. Traditional multi-drug treatment for poisoning by OPs consist of a combination of drugs such as carbamates (e.g. pyridostigmine), antimuscarinics, reactivators of inhibited AChE and anti-convulsants in postexposure modalities. These treatments, however, are far from optimal and do not prevent respiratory stress, tremors, convulsions and behavioral impairments. In recent years, exogenous administration of “self” native enzyme scavengers e.g. cholinesterases (ChE) have been successfully used in many species (mice, rats and monkeys) as safe and efficacious prophylactic and post exposure treatments due to their capacity to scavenge OPs in the blood and rapidly detoxify the active components before inhibition of the endogenous targets can occur. Such bioscavengers are shown to be highly stable, specific and efficient, to have long half-lives in homologous systems and capable of functioning under physiological conditions without producing immunological or other adverse side effects. In addition to nerve agents, certain bioscavengers can be also used to neutralize drugs such as cocaine, heroin and succinylcholine (a cause of apnea).